World Health Organization estimates that there are about 2 billion patients infected with hepatitis B virus in the world, and 0.35-0.4 billion of them are chronic patients infected with HBV. Deaths due to acute or chronic HBV infection have reached 113.13 million every year and are increasing. There are a large number of hepatitis B patients in China and account for one-third of the number of chronic patients infected with HBV of the world, wherein, there are 0.12 billion hepatitis B carriers. Data shows that infection of hepatitis B virus has become a major disease endangering human health, therefore, an anti-HBV therapy effective in patients infected with HBV is particularly in urgent need worldwide, especially in China. In studies about treatment of HBV infection at home and abroad, it is considered that, persistent infection of HBV is the main reason for hepatitis B chronicity, and may lead to progression and deterioration of the disease into cirrhosis or HBV related hepatocellular carcinoma. Therefore, inhibition of HBV replication is the key to the treatment of chronic hepatitis B. At present, main drugs used for treatment of hepatitis B clinically can mainly be divided, according to their structures, sources and functions, into interferons, nucleosides, immunomodulators and natural herbs.
Hepatitis C virus (HCV) is a major cause for chronic liver diseases. There is no vaccine used for preventing HCV infection. The combination of long-term PEG IFN-α and Ribavirin (RBV) is the best drug used for treatment of hepatitis C in recent 10 years, but more than 50% of patents infected with type I HCV failed to respond to such combinational antiviral therapy. Moreover, IFN and RBV have great toxic and side effects and the course of treatment is up to 1 year, which greatly limite its clinical use. Meanwhile, some anti-HCV medicaments inhibiting protease NS3/NS5 are also in clinical trials in recent years.
Wnt signaling pathways are highly evolutionarily conserved in organism and regulate many life courses. During early development of animals, Wnt signaling is responsible for a series of important events such as ventral axis formation, blastoderm establishment, somite differentiation, tissue or organ formation, and directly controls cell fates such as proliferation, differentiation, polarization, apoptosis and anti-apoptosis. More than 10 members of the Wnt proteins are involved in various signal transduction pathways via interacting with different receptors on cell membrane. These pathways are divided into classical Wnt signaling pathway depending on β-catenin/TCF transcription complex (Wnt/β-catenin pathway) and non-classical Wnt signaling pathway independing on β-catenin/TCF transcription complex (Wnt/Ca2+ pathway and Wnt/JNK pathway).
Because Wnt/β-catenin signaling pathway is associated with many cancers and diseases, regulation of uncontrolled Wnt/β-catenin signaling pathway can be an excellent means for treating diseases related to Wnt/β-catenin signaling pathway. For example, the pathologic process of Alzheimer's disease is accompanied by abnormal inactivation of Wnt/β-catenin signaling pathway. Presenilin associated closely with Alzheimer's disease can form a complex with β-catenin and GSK3. Hence, molecular targeted therapies directed to the signaling pathways are expected to be a new and effective way for treatment of related diseases. In addition, Wnt signaling pathway also functions in maintaining pluripotency of stem cells, so adjustments of the signaling pathway are expected to be a new and effective way for application of stem cells.
Therefore, it is in urgent need to develop new drugs for treatment of hepatitis B, hepatitis C, and diseases associated with activity of Wnt signaling pathway.